The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations. This work aims to develop a novel approach for the protection of space pharmaceutical drug molecules from the radiation-induced damage to help extend or at least preserve their structural integrity and potency. To achieve this, free radical scavenging antioxidant, Trolox was conjugated on the surface of poly-lactic-co-glycolic acid (PLGA) nanoparticles for the protection of a candidate drug, melatonin that is used as a sleep aid medication in International Space Station (ISS). Melatonin-PLGA-PLL-Trolox nanoparticle as named as PolyRad was synthesized employing single oil in water (o/w) emulsion solvent evaporation method. PolyRad is spherical in shape and has an average diameter of ~600 nm with a low polydispersity index of 0.2. PolyRad and free melatonin (control) were irradiated by UV light after being exposed to a strong oxidant, hydrogen peroxide (H 2 o 2). Bare melatonin lost ~80% of the active structure of the drug following irradiation with UV light or treatment with H 2 o 2. In contrast, PolyRad protected >80% of the active structure of melatonin. The ability of PolyRad to protect melatonin structure was also carried out using 0, 1, 5 and 10 Gy gamma radiation. Gamma irradiation showed >98% active structures of melatonin encapsulated in PolyRads. Drug release and effectiveness of melatonin using PolyRad were evaluated on human umbilical vein endothelial cells (HUVEC) in vitro. Non-irradiated PolyRad demonstrated maximum drug release of ~70% after 72 h, while UV-irradiated and H 2 o 2-treated PolyRad showed a maximum drug release of ~85%. Cytotoxicity of melatonin was carried out using both live/dead and MTT assays. Melatonin, non-radiated PolyRad and irradiated PolyRad inhibited the viability of HUVEC in a dosedependent manner. Cell viability of melatonin, PolyRad alone without melatonin (PolyRad carrier control), non-radiated PolyRad, and irradiated PolyRad were ~98, 87, 75 and 70%, respectively at a concentration ~ 0.01 mg ml / (g ml 10 /). Taken together, PolyRad nanoparticle provides an attractive formulation platform for preventing damage to pharmaceutical drugs in potential space mission applications. As NASA prepares for exploration missions beyond low Earth orbit with no opportunities for resupply, pharmaceutical instability may present significant risk to the crew health due to the loss of efficacy over time. Astronauts suffer from sleep disruption during space flight that can affect their mental and physical health in performing routine work 1-4. Therefore, mitigation against the effects of space radiation on pharmaceutical drugs is necessary for the success of long-term space missions. NASA is primarily concerned with the he...

Heteromer star-shaped nanoparticles have the potential to carry out therapeutic agents, improve intracellular uptake, and safely release drugs after prolonged periods of residence at the diseased site. A one-step seed mediation process was employed using polylactide-co-glycolic acid (PLGA), polyvinyl alcohol (PVA), silver nitrate, and tetrakis(hydroxymethyl)phosphonium chloride (THPC). Mixing these reagents followed by UV irradiation successfully produced heteromer nanostars containing a number of arm chains attached to a single core with a high yield. The release of THPC from heteromer nanostars was tested for its potential use for breast cancer treatment. The nanostars present a unique geometrical design exhibiting a significant intracellular uptake by breast cancer cells but low cytotoxicity that potentiates its efficacy as drug carriers.